FGR的胎盘组织印记基因PEG10DNA甲基化水平及其意义
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摘要
目的通过检测父方表达印记基因PEG10 DNA在胎儿生长受限(FGR)患者胎盘组织甲基化水平,探索FGR是否与其胎盘中印记基因的甲基化程度相关。方法采用前瞻性研究,收集2014年1月至2017年1月在上海市第一人民医院宝山分院妇产科住院分娩的FGR者56例(研究组)和同期正常单胎晚孕分娩者56例(对照组),采用亚硫酸氢盐测序法(BSP)检测研究组和对照组胎盘组织的PEG10 DNA甲基化水平,分析其甲基化水平与FGR的临床病理关系。结果 FGR胎盘组织印记基因PEG10表现为异常甲基化水平,与对照组相比,研究组胎盘组织印记基因PEG10 DNA甲基化水平在CPG岛1无明显差异,而在CPG岛2及CPG岛3明显高于对照组(t值分别为94.97,7.16,均P<0.05),尤其以CPG岛2最为明显(研究组表达为0.544±0.027,对照组表达为0.152±0.015)。结论胎盘组织父方表达的印记基因的DNA甲基化水平可能是导致FGR发病的原因之一。
Objective To investigate the relationship between methylation state of imprinted gene(PEG10)paternally expressed gene 10 DNA in patient's placental tissues with fetal growth restriction(FGR) by detecting the methylation level of father's PEG 10 DNA in placental tissues. Methods Prospective study was conducted on the clinical date of 56 women with FGR(case group) delivering in Baoshan Branch of Shanghai First People's Hospital during January 2014 to January 2017 as well as 56 normal pregnant women with single birth(control group). Hydrogen sulfite sequencing(BSP) was used to evaluate DNA methylation levels of PEG10 in placental tissues, and the clinicpathological relationship between methylation level and FGR was analyzed. Results The characteristic of imprinted genes PEG10 was abnormal methylation of FGR in placental tissue. Compared with the control group, there was no significant difference in the level of DNA methylation of the placenta imprinting gene PEG10 in CPG Island 1, whereas the level in CPG Island 2 and CPG Island 3 was significantly higher in the case group( CPG Island 2 t=94.97, CPG Island 3 t=7.16, both P<0.05). CPG Island 2 was most obvious(0.544±0.027 in case group and 0.152 0.015 in the control group). Conclusion Methylation's level of the imprinted gene expressed in father in placental tissue might be one of the causes of FGR.
Objective To investigate the relationship between methylation state of imprinted gene(PEG10)paternally expressed gene 10 DNA in patient's placental tissues with fetal growth restriction(FGR) by detecting the methylation level of father's PEG 10 DNA in placental tissues. Methods Prospective study was conducted on the clinical date of 56 women with FGR(case group) delivering in Baoshan Branch of Shanghai First People's Hospital during January 2014 to January 2017 as well as 56 normal pregnant women with single birth(control group). Hydrogen sulfite sequencing(BSP) was used to evaluate DNA methylation levels of PEG10 in placental tissues, and the clinicpathological relationship between methylation level and FGR was analyzed. Results The characteristic of imprinted genes PEG10 was abnormal methylation of FGR in placental tissue. Compared with the control group, there was no significant difference in the level of DNA methylation of the placenta imprinting gene PEG10 in CPG Island 1, whereas the level in CPG Island 2 and CPG Island 3 was significantly higher in the case group( CPG Island 2 t=94.97, CPG Island 3 t=7.16, both P<0.05). CPG Island 2 was most obvious(0.544±0.027 in case group and 0.152 0.015 in the control group). Conclusion Methylation's level of the imprinted gene expressed in father in placental tissue might be one of the causes of FGR.
引文
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[14]Wang D, Wang G, Yang H, et al.DNA methylation modulates H19 and IGF2 expression in porcine female eye[J].Genet Mol Biol,2017,40(1):153-159.
[2]Mullins E, Prior T, Roberts I, et al.Changes in the maternal cytokine profile in pregnancies complicated by fetal growth restriction[J].Am J Reprod Immunol,2012,68(1):1-7.
[3]Longtine M S, Nelson D M.Placental dysfunction and fetal programming:the importance of placental size, shape, histopathology, and molecular composition[J].Semin Reprod Med,2011,29(3):187-196.
[4]Furuya M, Kurasawa K, Nagahama K, et al.Disrupted balance of angiogenic and antiangiogenic signalings in preeclampsia[J].J Pregnancy,2011,67(4):86-92.
[5]Diplas A I, Lambertini L, Lee M J, et al.Differential expression of imprinted genes in normal and IUGR human placentas[J].Epigenetics,2009,4(4):235-240.
[6]Cuckle H, von Dadelszen P,Ghidini A.Current controversies in prenatal diagnosis 4:pregnancy complications due to placental vascular disease(preeclampsia, FGR): are we ready for prevention?[J].Prenat Diagn,2013,33(1):17-20.
[7]吴瑜,冯旭,高岚,等.印记基因:发育中的重要调节因子[J].遗传,2016,38(6):508-522.
[8]Choux C, Binquet C, Carmignac V, et al.The epigenetic control of transposable elements and imprinted genes in newborns is affected by the mode of conception:ART versus spontaneous conception without underlying infertility[J].Hum Reprod,2018,33(2):331-340.
[9]Gourvas V, Dalpa E, Konstantinidou A, et al.Angiogenic factors in placentas from pregnancies complicated by fetal growth restriction(review)[J].Mol Med Rep,2012,6(1):23-27.
[10]Janssen A B, Tunster S J, Savory N, et al.Placental expression of imprinted genes varies with sampling site and mode of delivery[J].Placenta,2015,36(8):790-795.
[11]Boot A, Oosting J, de Miranda N F, et al.Imprinted survival genes preclude loss of hetero zygosity of chromosome 7 in cancer cells[J].J Pathol,2016,240(1):72-83.
[12]Liu L, Wang Y X, Shen C, et al.Benzo(a) pyrene inhibits migration and invasion of extra villous trophoblast HTR‐8/SVneo cells via activation of the ERK and JNK pathway[J].J Applied Toxicology,2016,36(7):946-955.
[13]Liang X Y, Chen X, Jin Y Z, et al.Expression and significance of the imprinted gene PEG10 in placenta of patients with preeclampsia[J].Genet Mol Res,2014,13(4):10607-10614.
[14]Wang D, Wang G, Yang H, et al.DNA methylation modulates H19 and IGF2 expression in porcine female eye[J].Genet Mol Biol,2017,40(1):153-159.